US11447505B1ActiveUtility

Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer

71
Assignee: CANCER RESEARCH TECH LTDPriority: Aug 18, 2017Filed: Aug 17, 2018Granted: Sep 20, 2022
Est. expiryAug 18, 2037(~11.1 yrs left)· nominal 20-yr term from priority
C07D 487/10C07D 471/04C07D 487/04C07D 471/10C07D 519/00A61P 35/04C07F 7/0812
71
PatentIndex Score
2
Cited by
6
References
15
Claims

Abstract

The present application relates to a compound of Formula I, or a salt, hydrate or solvate thereof, as defined herein. The present compounds are found to have pharmacological effects, particularly at MRCK. Further provided are pharmaceutical compositions comprising said compounds. The present invention also relates to the use of these compounds as therapeutic agents, in particular, for the treatment and/or prevention of proliferative diseases, such as cancer.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A compound of Formula I, or a salt, hydrate or solvate thereof; 
       
         
           
           
               
               
           
         
         wherein,
 R 4  is a group of formula II, 
 
       
       
         
           
           
               
               
           
         
         
           R 3  is selected from 5-15 membered heteroaryl, where said 5-15 membered heteroaryl is optionally substituted by one or more R b ; 
           each R b  is selected from hydrogen, hydroxyl, halogen, CN, C 1-6  alkyl and O—C 1-6  alkyl; wherein said C 1-6  alkyl is optionally substituted with one or more groups selected from hydroxyl, halogen, ═O, NR c R d , C 1-6  alkyl, O—C 1-6  alkyl, and phenyl; 
           each R c  is independently selected from hydrogen and C 1-6  alkyl; 
           each R d  is independently selected from hydrogen, CN, C 1-6  haloalkyl, O—C 1-6  haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6  alkyl, O—C 1-6  alkyl and phenyl, wherein said C 1-6  alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered heterocycloalkyl and C 3-6  cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, CN, NH 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl, 3-7 membered heterocycloalkyl, C 3-10 alkylheterocycloalkyl, C 1-6  alkyl and O—C 1-6  alkyl; or 
           R c  and R d , when attached to the same atom, together with the atom to which they are attached form a 3-7 membered heterocycloalkyl ring optionally substituted by one or more groups selected from hydroxyl, halogen, CN, NH 2 , NH(C 1-6 alkyl), N(C 1-6  alkyl) 2 , C 1-6  haloalkyl, O—C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl, 3-7 membered heterocycloalkyl, C 1-6  alkyl and O—C 1-6  alkyl; 
           R 5  is selected from hydrogen, halogen, hydroxyl, NH 2 , NH(C 1-6  alkyl), N(C 1-6  alkyl) 2 , C 1-6  alkyl, O—C 1-6  alkyl, C 1-6  haloalkyl, O—C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl and CN; 
           R 9  and R 10  are independently selected from hydroxyl, C 1-6  alkyl, O—C 1-6  alkyl, C 1-6  haloalkyl, C 1-6 haloalkoxy, NH 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , NR c R d , NR c C(═O)R d , C(O)NR c R d , phenyl, and 3-7 membered heterocycloalkyl, where said C 1-6  alkyl, phenyl and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from halogen, hydroxyl, CN, NH 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , C 1-6  alkyl, O—C 1-6  alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 3-6  cycloalkyl and phenyl; or 
           R 9  and R 10  together with the carbon atom to which they are attached form a 4-6 membered heterocycloalkyl ring comprising at least one heteroatom selected from O, N and S, where said heterocycloalkyl ring is optionally substituted with one or more R m ; 
           R m  is selected from hydroxyl, halogen, CN, C 1-6  alkyl, C 3-6  cycloalkyl, C 1-6  haloalkyl, and OR a ; where R a  is defined above; and 
           n is a number selected from 0 and 1. 
         
       
     
     
       2. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, wherein R 4  is selected from 
       
         
           
           
               
               
           
         
         where each is optionally substituted on a carbon atom by one or more R i , wherein R j  is selected from halogen, C 1-6  alkyl, hydroxyl and O—C 1-6  alkyl with the proviso that R j  is selected from halogen and C 1-6  alkyl when bonded to a carbon adjacent to N. 
       
     
     
       3. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, wherein R 9  and R 10  are independently selected from hydroxyl, C 1-6  alkyl, NH 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , NR c R d , NR c C(═O)R d , C(O)NR c R d , phenyl, and 3-7 membered heterocycloalkyl, where said C 1-6  alkyl, phenyl and 3-7 membered heterocycloalkyl are optionally substituted with one or more groups selected from halogen, hydroxyl, CN, NH 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , C 1-6  alkyl, O—C 1-6  alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 3-6  cycloalkyl and phenyl; or
 R 9  and R 10  together with the carbon atom to which they are attached form a 4-6 membered heterocycloalkyl ring comprising at least one heteroatom selected from O, N and S, where said heterocycloalkyl ring is optionally substituted with one or more R m . 
 
     
     
       4. The compound according to any  claim 1 , or a salt, hydrate or solvate thereof, wherein R m  is selected from C 1-3  alkyl. 
     
     
       5. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, wherein R 3  is selected from 5-6 membered heteroaryl, where said 5-6 membered heteroaryl is optionally substituted by one or more R b . 
     
     
       6. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, wherein R 3  is a 6 membered heteroaryl optionally substituted by one or more R b . 
     
     
       7. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, wherein R 3  is 
       
         
           
           
               
               
           
         
         optionally substituted by one or two R b  groups. 
       
     
     
       8. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, wherein R b  is selected from hydrogen and C 1-3  alkyl. 
     
     
       9. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, wherein R 5  is selected from hydrogen, halogen, hydroxyl, C 1-6  alkyl, O—C 1-6  alkyl, C 1-6  haloalkyl, O—C 1-6  haloalkyl, C 3-6  cycloalkyl, phenyl and CN. 
     
     
       10. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, of sub-formula Ic′: 
       
         
           
           
               
               
           
         
         wherein
 ring A is a heteroaryl group selected from a pyrimidine, thiazole, thiadiazole, isothiazole, pyridazine, pyridine and pyrazine; 
 m is a number selected from 0, 1 and 2; and 
 n, R 9  and R 10  are as defined in  claim 1 . 
 
       
     
     
       11. The compound according to  claim 10 , or a salt, hydrate or solvate thereof, wherein R 9  and R 10  together with the carbon atom to which they are attached form a 5-6 membered heterocycloalkyl ring comprising one nitrogen atom, where said heterocycloalkyl ring is optionally substituted with one or more R m  as defined in  claim 1 . 
     
     
       12. The compound according to  claim 1 , or a salt, hydrate or solvate thereof, selected from: 
       
         
           
                 
                 
               
                     
                 
                   E114 
                   4-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]isothiazole 
                 
                   E115 
                   3-[4-[(6R)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]-1,2,4-thiadiazole 
                 
                   E116 
                   3-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]-1,2,4-thiadiazole 
                 
                   E117 
                   (6S)-8-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E118 
                   (6R)-8-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E119 
                   3-[4-[(6R)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]isothiazole 
                 
                   E120 
                   3-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]isothiazole 
                 
                   E121 
                   3-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin- 
                 
                     
                   3-yl]isothiazole 
                 
                   E122 
                   (6S)-8-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E123 
                   4-[(5R)-1,7-diazaspiro[4.4]nonan-7-yl]-3-pyrimidin-5-yl-1H- 
                 
                     
                   pyrrolo[2,3-b]pyridine 
                 
                   E124 
                   4-[(5S)-1,7-diazaspiro[4.4]nonan-7-yl]-3-pyrimidin-5-yl-1H- 
                 
                     
                   pyrrolo[2,3-b]pyridine 
                 
                   E125 
                   (5R)-2-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,6- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E126 
                   (5S)-2-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,6- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E127 
                   (5R)-2-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,6- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E128 
                   (5S)-2-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,6- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E129 
                   3-[4-(2,6-diazaspiro[4.5]decan-2-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-1,2,4-thiadiazole 
                 
                   E130 
                   2-[4-[(5R)-2,6-diazaspiro[4.5]decan-2-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]-5-methyl-thiazole 
                 
                   E131 
                   2-[4-[(5S)-2,6-diazaspiro[4.5]decan-2-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]-5-methyl-thiazole 
                 
                   E132 
                   2-[4-[(5R)-2,6-diazaspiro[4.5]decan-2-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]thiazole 
                 
                   E133 
                   2-[4-[(5S)-2,6-diazaspiro[4.5]decan-2-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]thiazole 
                 
                   E134 
                   2-[4-[(5S)-1,7-diazaspiro[4.4]nonan-7-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]thiazole 
                 
                   E135 
                   2-[4-[(5R)-1,7-diazaspiro[4.4]nonan-7-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]thiazole 
                 
                   E136 
                   3-[4-(1,7-diazaspiro[4.4]nonan-7-yl)-1H-pyrrolo[2,3-b]pyridin- 
                 
                     
                   3-yl]isothiazole 
                 
                   E137 
                   4-(1,7-diazaspiro[4.4]nonan-7-yl)-3-(2-pyridyl)-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridine 
                 
                   E138 
                   8-[3-(2-pyridyl)-1H-pyrrolo[2,3,b]pyridin-4-yl]-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E139 
                   (6S)-8-[3-(2-pyridyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E140 
                   (6R)-8-[3-(2-pyridyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E141 
                   2-[3-(2-pyridyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-2,6- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E142 
                   3-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin- 
                 
                     
                   3-yl]-4-methyl-isothiazole 
                 
                   E143 
                   2-[4-(1,9-diazaspiro[4.5]decan-9-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-5-methyl-thiazole 
                 
                   E144 
                   2-[4-(2,6-diazaspiro[4.5]decan-2-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-5-methyl-thiazole 
                 
                   E146 
                   2-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]-5-methyl-thiazole 
                 
                   E147 
                   2-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-5-methyl-thiazole 
                 
                   E148 
                   2-[4-[(6R)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]-5-methyl-thiazole 
                 
                   E149 
                   2-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]thiazole 
                 
                   E150 
                   2-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]thiazole 
                 
                   E151 
                   2-[4-[(6R)-1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]thiazole 
                 
                   E152 
                   2-[4-(1,7-diazaspiro[3.4]octan-7-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-5-methyl-thiazole 
                 
                   E153 
                   2-[4-(1,8-diazaspiro[3.5]nonan-8-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-5-methyl-thiazole 
                 
                   E154 
                   2-[4-(1,7-diazaspiro[4.4]nonan-7-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]thiazole 
                 
                   E155 
                   2-[4-(2,6-diazaspiro[4.5]decan-2-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]thiazole 
                 
                   E156 
                   4-(2,6-diazaspiro[3.5]nonan-6-yl)-3-pyridazin-4-yl-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridine 
                 
                   E157 
                   8-(3-pyrimidin-2-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E158 
                   2-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-4-methyl-thiazole 
                 
                   E159 
                   4-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-2-methyl-thiazole 
                 
                   E160 
                   8-[3-(2-methylpyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E161 
                   4-(1,7-diazaspiro[4.4]nonan-7-yl)-3-pyridazin-4-yl-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridine 
                 
                   E162 
                   2-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,6- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E163 
                   7-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,7- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E164 
                   4-(2,7-diazaspiro[4.4]nonan-2-yl)-3-pyridazin-4-yl-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridine 
                 
                   E166 
                   8-[3-(2-methylpyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E167 
                   4-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-3,5-dimethyl-isoxazole 
                 
                   E168 
                   8-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E169 
                   8-[3-(3-fluoro-2-pyridyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8-  
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E170 
                   8-[3-(5-fluoro-2-pyridyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E171 
                   8-[3-(5-fluoro-3-pyridyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8-  
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E172 
                   8-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E173 
                   (6R)-8-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E174 
                   (6S)-8-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E175 
                   8-(3-pyridazin-3-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E176 
                   3-methyl-1-(3-thiazol-2-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)- 
                 
                     
                   piperidin-3-amine 
                 
                   E177 
                   3-ethyl-1-[3-(5-methylthiazol-2-yl)-1H-pyrrolo[2,3-b]pyridin-4- 
                 
                     
                   yl]piperidin-3-amine 
                 
                   E178 
                   3-methyl-1-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-  
                 
                     
                   yl)-piperidin-3-amine 
                 
                   E188 
                   8-[3-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E189 
                   8-(3-pyrazin-2-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E191 
                   2-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,8- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E192 
                   (6R)-8-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E194 
                   2-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E195 
                   9-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,9- 
                 
                     
                   diazaspiro[4.5]decane 
                 
                   E196 
                   8-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8- 
                 
                     
                   diazaspiro[5.5]undecane 
                 
                   E206 
                   (6S)-1-methyl-8-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4- 
                 
                     
                   yl)-1,8-diazaspiro[5.5]undecane 
                 
                   E207 
                   (6S)-1-ethyl-8-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4- 
                 
                     
                   yl)-1,8-diazaspiro[5.5]undecane 
                 
                   E208 
                   (6R)-1-ethyl-8-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4- 
                 
                     
                   yl)-1,8-diazaspiro[5.5]undecane 
                 
                   E209 
                   2-[4-(1-ethyl-1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]thiazole 
                 
                   E210 
                   2-[4-(1-ethyl-1,8-diazaspiro[5.5]undecan-8-yl)-1H-pyrrolo[2,3- 
                 
                     
                   b]pyridin-3-yl]-5-methyl-thiazole 
                 
                   E236 
                   3-[4-[1,8-diazaspiro[5.5]undecan-8-yl]-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-1,2,4-thiadiazole 
                 
                   E237 
                   2-[4-(1,7-diazaspiro[4.4]nonan-7-yl)-1H-pyrrolo[2,3-b]pyridin-3- 
                 
                     
                   yl]-5-methyl-thiazole. 
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
       13. A pharmaceutical composition which comprises a compound according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and one or more pharmaceutically acceptable excipients. 
     
     
       14. A combination comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       15. The compound of  claim 1 , or a salt, hydrate or solvate thereof, selected from: 
       
         
           
                 
                 
                 
               
                     
                 
                     
                   Structure 
                   IUPAC Name 
                 
                     
                 
                   E116 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]- 1H-pyrrolo[2,3-b]pyridin-3-yl]-1,2,4-thiadiazole 
                 
                     
                 
                   E120 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]- 1H-pyrrolo[2,3-b]pyridin-3-yl]isothiazole 
                 
                     
                 
                   E117 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (6S)-8-(3-pyrimidin-4-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)-1,8-diazaspiro[5.5]undecane 
                 
                     
                 
                   E150 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]- 1H-pyrrolo[2,3-b]pyridin-3-yl]thiazole 
                 
                     
                 
                   E174 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (6S)-8-(3-pyridazin-4-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)-1,8-diazaspiro[5.5]undecane 
                 
                     
                 
                   E206 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (6S)-1-methyl-8-(3-pyrimidin-4-yl-1H- pyrrolo[2,3-b]pyridin-4-yl)-1,8- diazaspiro[5.5]undecane 
                 
                     
                 
                   E133 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-[(5S)-2,6-diazaspiro[4.5]decan-2-yl]-1H- pyrrolo[2,3-b]pyridin-3-yl]thiazole 
                 
                     
                 
                   E209 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-(1-ethyl-1,8-diazaspiro[5.5]undecan-8-yl)- 1H-pyrrolo[2,3-b]pyridin-3-yl]thiazole 
                 
                     
                 
                   E139 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (6S)-8-[3-(2-pyridyl)-1H-pyrrolo[2,3-b]pyridin- 4-yl]-1,8-diazaspiro[5.5]undecane 
                 
                     
                 
                   E207 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (6S)-1-ethyl-8-(3-pyrimidin-4-yl-1H- pyrrolo[2,3-b]pyridin-4-yl)-1,8- diazaspiro[5.5]undecane 
                 
                     
                 
                   E146 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-[(6S)-1,8-diazaspiro[5.5]undecan-8-yl]- 1H-pyrrolo[2,3-b]pyridin-3-yl]-5-methyl- thiazole 
                 
                     
                 
                   E126 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (5S)-2-(3-pyrimidin-5-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)-2,6-diazaspiro[4.5]decane 
                 
                     
                 
                   E131 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-[(5S)-2,6-diazaspiro[4.5]decan-2-yl]-1H- pyrrolo[2,3-b]pyridin-3-yl]-5-methyl-thiazole 
                 
                     
                 
                   E210 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-(1-ethyl-1,8-diazaspiro[5.5]undecan-8-yl)- 1H-pyrrolo[2,3-b]pyridin-3-yl]-5-methyl- thiazole 
                 
                     
                 
                   E171 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   8-[3-(5-fluoro-3-pyridyl)-1H-pyrrolo[2,3- b]pyridin-4-yl]-1,8-diazaspiro[5.5]undecane 
                 
                     
                 
                   E168 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   8-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4- yl)-1,8-diazaspiro[5.5]undecane 
                 
                     
                 
                   E128 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (5S)-2-(3-pyrimidin-4-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)-2,6-diazaspiro[4.5]decane 
                 
                     
                 
                   E114 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H- pyrrolo[2,3-b]pyridin-3-yl]isothiazole 
                 
                     
                 
                   E155 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-(2,6-diazaspiro[4.5]decan-2-yl)-1H- pyrrolo[2,3-b]pyridin-3-yl]thiazole 
                 
                     
                 
                   E236 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-[4-[1,8-diazaspiro[5.5]undecan-8-yl]-1H- pyrrolo[2,3-b]pyridin-3-yl]-1,2,4-thiadiazole 
                 
                     
                 
                   E176 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-methyl-1-(3-thiazol-2-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)piperidin-3-amine 
                 
                     
                 
                   E170 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   8-[3-(5-fluoro-2-pyridyl)-1H-pyrrolo[2,3- b]pyridin-4-yl]-1,8-diazaspiro[5.5]undecane 
                 
                     
                 
                   E169 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   8-[3-(3-fluoro-2-pyridyl)-1H-pyrrolo[2,3- b]pyridin-4-yl]-1,8-diazaspiro[5.5]undecane 
                 
                     
                 
                   E136 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-[4-(1,7-diazaspiro[4.4]nonan-7-yl)-1H- pyrrolo[2,3-b]pyridin-3-yl]isothiazole 
                 
                     
                 
                   E178 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-methyl-1-(3-pyrimidin-5-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)piperidin-3-amine 
                 
                     
                 
                   E142 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-[4-(1,8-diazaspiro[5.5]undecan-8-yl)-1H- pyrrolo[2,3-b]pyridin-3-yl]-4-methyl-isothiazole 
                 
                     
                 
                   E129 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-[4-(2,6-diazaspiro[4.5]decan-2-yl)-1H- pyrrolo[2,3-b]pyridin-3-yl]-1,2,4-thiadiazole 
                 
                     
                 
                   E134 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   2-[4-[(5S)-1,7-diazaspiro[4.4]nonan-7-yl]-1H- pyrrolo[2,3-b]pyridin-3-yl]thiazole 
                 
                     
                 
                   E122 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   (6S)-8-(3-pyrimidin-5-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)-1,8-diazaspiro[5.5]undecane.

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